Research from the University of Southern California (USC) has discovered a new mechanism to allow embryonic stem cells to divide indefinitely and remain undifferentiated. The study, which will be published in the May 22 issue of the journal Nature, also reveals how embryonic stem cell multiplication is regulated, which may be important in understanding how to control tumor cell growth.
"Our study suggests that what we believe about how embryonic stem cell self-renewal is controlled is wrong," says Qi-Long Ying, Ph.D., assistant professor of Cell and Neurobiology at the Keck School of Medicine of USC, researcher at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, and lead author of the paper. "Our findings will likely change the research direction of many stem cell laboratories."
Contrary to the current understanding of stem cell self-renewal and differentiation, the findings suggest that embryonic stem cells will remain undifferentiated if they are shielded from differentiation signals. By applying small molecules that block the chemicals from activating the differentiation process, the natural default of the cell is to self-renew, or multiply, as generic stem cells.
"This study presents a completely new paradigm for understanding how to grow embryonic stem cells in the laboratory," says Martin Pera, Ph.D., director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. "The discovery has major implications for large scale production of specialized cells, such as brain, heart muscle and insulin producing cells, for future therapeutic use."
Embryonic stem cells have only been derived from a very small number of species.
"We believe the process we discovered in mice may facilitate the derivation of embryonic stem cells from species like pigs, cows or other large animals, which have not been done before," continues Ying. "If deriving embryonic stem cells from cows, for instance, is possible, then perhaps in the future cows might be able to produce milk containing medicines."
With better understanding of the multiplication process of embryonic stem cells, researchers have additional insight on tumor cell growth as these cells share similar qualities. "Our study reveals part of the little known process of how embryonic stem cells multiplication is regulated. This is important for us in understanding how to control tumor cell growth moving forward in cancer research," says Ying.
This research was funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council of the UK, the Canadian Institutes of Health Research, and by the European Commission Framework VI project EuroStemCell. Philip Cohen is a Royal Society Research Professor and Austin Smith is a Medical Research Council Professor.
- Qi-Long Ying, Jason Wray, Jennifer Nichols, Laura Batlle-Morera, Bradley Doble, James Woodgett, Philip Cohen and Austin Smith. "The Ground State of Embryonic Stem Cell Self-Renewal," Nature (2008). Doi: 10.1038/nature06968.
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